Genetic Variant NM_032849.4:c.191C>G (chr13-30906706-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032849.4(MEDAG):c.191C>G(p.Ala64Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,518,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

MEDAG
NM_032849.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0120

Publications

1 publications found

Variant links:

Genes affected

MEDAG (HGNC:25926): (mesenteric estrogen dependent adipogenesis) Predicted to be involved in positive regulation of fat cell differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MEDAG links:

TEX26-AS1 (HGNC:42784): (TEX26 antisense RNA 1)

TEX26-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077637106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEDAG	NM_032849.4	MANE Select	c.191C>G	p.Ala64Gly	missense	Exon 1 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1438-22646G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEDAG	ENST00000380482.9	TSL:1 MANE Select	c.191C>G	p.Ala64Gly	missense	Exon 1 of 5	ENSP00000369849.4	Q5VYS4-1
MEDAG	ENST00000904728.1		c.191C>G	p.Ala64Gly	missense	Exon 1 of 5	ENSP00000574787.1
MEDAG	ENST00000968515.1		c.191C>G	p.Ala64Gly	missense	Exon 1 of 3	ENSP00000638574.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1366454

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

674146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29482

American (AMR)

AF:

0.00

AC:

AN:

32988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23130

East Asian (EAS)

AF:

0.00

AC:

AN:

35334

South Asian (SAS)

AF:

0.0000133

AC:

AN:

75252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4982

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074178

Other (OTH)

AF:

0.00

AC:

AN:

56904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.39

M_CAP

Benign

0.015

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.012

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

REVEL

Benign

0.075

Sift

Benign

0.15

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.091

MutPred

0.55

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.076

MPC

0.12

ClinPred

0.049

GERP RS

-0.35

PromoterAI

-0.095

Neutral

(source)

Varity_R

0.092

gMVP

0.25

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over